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Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling
Published on: August 1, 2016
Local control in cardiac E-C coupling
M B Cannell1, Cherrie H T Kong
1School of Physiology & Pharmacology, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK. mark.cannell@bristol.ac.uk
Journal of Molecular and Cellular Cardiology
|May 19, 2011
Summary
Local control theory explains cardiac calcium release by spatially limiting regeneration through stochastic recruitment of calcium release units (CRUs). This ensures stable heart contraction without compromising sensitivity.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Physiology
Background:
- The calcium-induced calcium release (CICR) hypothesis explains cardiac excitation-contraction coupling.
- Regeneration in CICR presents challenges in controlling calcium release and force production.
Purpose of the Study:
- To explain how local control theory addresses regeneration issues in CICR.
- To elucidate the spatial uncoupling of calcium release units (CRUs) and their role in graded calcium release.
- To review mechanisms for CRU calcium release termination and suggest novel functions for sarcoplasmic reticulum calcium modulation.
Main Methods:
- Theoretical explanation of local control mechanisms in cardiac excitation-contraction coupling.
- Analysis of the spatial relationship between CRUs and their impact on calcium dynamics.
- Review of potential mechanisms for terminating calcium release from CRUs.
Main Results:
- Local control theory explains graded calcium release by spatially limiting regeneration through the stochastic recruitment of CRUs.
- The distance between CRUs partially uncouples them, limiting regenerative gain and ensuring stability.
- High local calcium levels near the surface membrane activate RyRs, while diffusion limits spread to adjacent CRUs.
Conclusions:
- Local control theory provides a framework for understanding cardiac calcium release and force production.
- Modulation of RyR gating may regulate sarcoplasmic reticulum calcium levels for metabolic functions beyond contractility.
- Further research is needed to clarify the termination mechanisms of CRU calcium release.
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